dl-3-n-Butylphthalide (NBP) also called butylphthalide is dl-3-butylisobenzofuran-1(3H)-one, which is a raceme. 1-3-n-Butylphthalid is extracted from celery seeds. NBP acts on multiple steps of cerebral ischemia procedure, such as reducing infarct area after focal cerebral ischemia, increasing cerebral blood flow in ischemic area and improving microcirculation in cerebral ischemic area, protecting mitochondrial function, alleviating damage to nerve function, and improving cerebral energy metabolism after total cerebral ischemia. Chinese Patent Nos. 98125618.X, 03137457.3, 200310100222.2 and 200410001748.X respectively disclose the applications of butylphthalide in anti-thrombus and anti-platelet aggregation, the application of 1-n-butylphthalide in prevention and treatment of dementia, cerebral infarction and in manufacture of medicaments for treatment of cerebral ischemia.
Currently butylphthalide preparations available in market are only soft capsules. Since butylphthalide is of an oily liquid form, it can be dissolved in an oil phase or directly processed to form an emulsion, then can be packaged in hard capsules or soft capsules, or can be orally administered directly. However, butylphthalide has a relatively apparent first pass effect which leads to a relatively low bioavailability. In addition, cerebral ischemia patients usually are companied with dysphagia or coma, so that capsules cannot meet the clinical requirements for these patients. For cerebral ischemia patients, time is life. Therefore, it is vital to develop a new delivery system suitable for clinical application.